The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Walter Herzog - One of the best experts on this subject based on the ideXlab platform.
-
Mechanics of Sarcomeres in Series and Instability - JURA Best Paper Award 2016-2017
Journal of Undergraduate Research in Alberta, 2017Co-Authors: Jared Collette, Azim Jinha, Walter HerzogAbstract:Sarcomeres are the smallest independent unit of force production in the muscle. Current theoretical models of Sarcomere in series, i.e. a myofibril, predict instability on the descending limb region of the force-length relationship. However, experimental evidence suggests that Sarcomeres can be stable on the descending limb region with non-uniform lengths. The models presented re-evaluates the assumption that Sarcomeres are independent units of contraction. Instead, it is hypothesized that there is a dependency between Sarcomeres for force generation. Sarcomeres in series were modelled, with force as the dependent variable and Sarcomere length and time as the independent variables. Models were developed with both independent and dependent Sarcomere force generation. The independent Sarcomere models resulted in instability that current theoretical models predict. Two cases of dependent Sarcomere models were implemented, both included a shift in the passive force with varying degrees of dependency between adjacent Sarcomeres. With these models, there was either stability with non-uniform length, stability with uniform length, or instability on the descending limb region of the force-length relationship. The major finding was that mathematically, Sarcomeres with a variable passive force can reach equilibrium at various lengths if a dependency between adjacent Sarcomeres is incorporated into the models.
-
Aging is Associated with Reductions in Fascicle Length, Sarcomere Length and Serial Sarcomere Loss
Journal of Undergraduate Research in Alberta, 2015Co-Authors: Sean Crooks, Geoffrey A. Power, Walter HerzogAbstract:Introduction: Aging is associated with decreased active force production leading to muscle weakness and subsequently decreased muscle performance. Aging also affects the muscle’s passive force properties; whereby in old age passive muscle force has been shown to be elevated above that of young, which may be related to increased muscle stiffness with age. The purpose of this study was to investigate potential structural property changes that occur in aged muscle that may contribute to increased passive force. Methods : The muscle length where peak force occurred (i.e. plateau of the force-length relationship (FL); L 0 ) was determined for the medial gastrocnemius muscle (MG) of young ( n = 9) and old rats ( n = 8) rats. Muscles were fixed at L 0 in 10% formalin , fascicle length, Sarcomere number and the Sarcomere length were compared at L 0. Results: Muscle from old rats showed a reduction of ~14% in fascicle length, ~4% in Sarcomere length and ~10% in Sarcomere number, ( P < 0.001). Discussion: Shorter fascicles and reduced Sarcomeres in series in muscle from old rats may explain increased passive forces in older individuals. Reduced Sarcomere number in series would lead to overstretched Sarcomeres, leading to increased tension on Sarcomere passive force structures and Sarcomeres operating on the descending limb of FL relationship.
-
CONTRACTILE PROTEIN NUMBER IN ADJACENT SarcomereS – IS THERE A DIFFERENCE?
Journal of Undergraduate Research in Alberta, 2014Co-Authors: Hilda Antwi-nsiah, Ruth A. Seerattan, Walter HerzogAbstract:INTRODUCTION Variation in Sarcomere length within an actively contracting skeletal muscle has often been observed yet remains unexplained. Sarcomeres within a myofibril are connected in series and thus they must each produce the same amount of force [1]. We know that the amount of force that a Sarcomere can produce is related to the amount of overlap between the actin and myosin filaments within it. As a result, Sarcomere length affects the amount of force that a Sarcomere can produce [2]. If we assume that Sarcomeres within a myofibril contain the same number of contractile proteins, it would be expected that Sarcomeres within a myofibril would be of the same or similar length thus producing the same amount of force. However, it has been observed that Sarcomere lengths vary within myofibrils [3] causing us to hypothesize that contractile protein number differs between adjacent Sarcomeres. The purpose of this study was to identify the number of myosin filaments in serially arranged Sarcomeres and determine if this number differed. The hope was to provide a possible explanation for the difference in serially arranged Sarcomere lengths within myofibrils. METHODS Bundles of rabbit psoas muscle fibers about 2 mm in diameter were harvested and placed in a modified Karnovsky’s fixative. The fibers were post fixed with 1% osmium tetroxide and then put through a standard dehydration and infiltration process. The muscle samples were teased apart under a dissecting scope to get bundles about 100 μm in diameter and embedded in Embed 812 Resin. Blocks were cut into 100 nm thick slices perpendicularly to the embedded samples to obtain cross sections of the muscle samples. Sectioning was done using an ultracut microtome. The sections were stained with uranyl acetate and lead citrate and viewed under an electron microscope to obtain images of myofibril cross sections. The number of myosin filaments present was then counted manually. RESULTS An electron micrograph of a Sarcomere cross section was obtained and is shown in Figure 1. The number of myosin filaments counted was 715 in this Sarcomere of approximate cross sectional area 0.7 μm 2 . LIMITATIONS Due to the size of our samples (about 100 μm in diameter) compared to the size of a single myofibril (about 1 μm in diameter) we were not able to follow a single myofibril in multiple micrographs and compare the number of myosin filaments in adjacent Sarcomeres. DISCUSSION AND CONCLUSIONS In this study we were successful in obtaining an electron micrograph of a Sarcomere in cross section and counting the number of myosin filaments within it. We anticipate that when we are successful in counting the number of myosin filaments in adjacent Sarcomeres, we will find a difference, thus providing a possible explanation for the variance in Sarcomere length within a myofibril. From this investigation we have identified a viable method for imaging Sarcomeres in cross section and counting the number of myosin filaments within them. The next step is to refine the protocol in order to embed smaller samples. With smaller samples it will be easier to locate and track a single myofibril in multiple electron micrographs and compare the number of myosin filaments in adjacent Sarcomeres.
-
An Examination of Sarcomere Length Non-Uniformities in Actively Stretched Muscle Myofibrils
Biophysical Journal, 2014Co-Authors: Kaleena Johnston, Azim Jinha, Walter HerzogAbstract:Residual force enhancement (RFE) is a characteristic of skeletal muscle describing the increase in force exhibited following an active stretch on the descending limb of the force-length relationship, compared to the force of an isometric contraction at the final length. It has previously been argued that RFE is a result of instable Sarcomeres on the descending limb, causing longer, weaker Sarcomeres to lengthen to a greater extent than shorter, stronger Sarcomeres, when a myofibril is actively stretched. If this were the mechanism of RFE, then Sarcomeres should become more non-uniform in length after an active stretch. The purpose of this study was to investigate length non-uniformities between Sarcomeres within a myofibril in isometric contractions pre- and post-active stretch. We hypothesized that Sarcomere lengths would be less uniform in the post-stretch condition. Rabbit psoas muscle myofibrils were stretched passively to an average Sarcomere length of 3.2 μm. The myofibrils were then activated. Five seconds after full activation, myofibrils were rapidly shortened to an average Sarcomere length of 2.4 μm, held at that length for ten seconds and then stretched back to 3.2 μm. Individual Sarcomere lengths were then determined during the initial isometric contraction and again following the active stretch. Standard deviations of Sarcomere lengths were compared to analyze non-uniformity. Preliminary results gave normalized Sarcomere length standard deviations of 5.7 % and 10.2 % for the initial isometric contraction and following active stretch respectively (103 % RFE). This supports the hypothesis that Sarcomere lengths might be less uniform after active stretch; however, further testing will increase the sample size to 20. This will allow for a more general idea of the development of Sarcomere length non-uniformities following active stretch and might provide additional insight into the mechanism of RFE.
-
Overextended Sarcomeres regain filament overlap following stretch.
Journal of Biomechanics, 2012Co-Authors: Appaji Panchangam, Walter HerzogAbstract:Abstract Sarcomere overextension has been widely implicated in stretch-induced muscle injury. Yet, Sarcomere overextensions are typically inferred based on indirect evidence obtained in muscle and fibre preparations, where individual Sarcomeres cannot be observed during dynamic contractions. Therefore, it remains unclear whether Sarcomere overextensions are permanent following injury-inducing stretch-shortening cycles, and thus, if they can explain stretch-induced force loss. We tested the hypothesis that overextended Sarcomeres can regain filament overlap in isolated myofibrils from rabbit psoas muscles. Maximally activated myofibrils ( n =13) were stretched from an average Sarcomere length of 2.6±0.04 μm by 0.9 μm Sarcomere −1 at a speed of 0.1 μm Sarcomere −1 s −1 and immediately returned to the starting lengths at the same speed (Sarcomere strain=34.1±2.3%). Myofibrils were then allowed to contract isometrically at the starting lengths (2.6 μm) for ∼30 s before relaxing. Force and individual Sarcomere lengths were measured continuously. Out of the 182 Sarcomeres, 35 Sarcomeres were overextended at the peak of stretch, out of which 26 regained filament overlap in the shortening phase while 9 (∼5%) remained overextended. About 35% of the Sarcomeres with initial lengths on the descending limb of the force-length relationship and ∼2% of the Sarcomeres with shorter initial lengths were overextended. These findings provide first ever direct evidence that overextended Sarcomeres can regain filament overlap in the shortening phase following stretch, and that the likelihood of overextension is higher for Sarcomeres residing initially on the descending limb.
Xu Zhang - One of the best experts on this subject based on the ideXlab platform.
-
A transcriptomics resource reveals a transcriptional transition during ordered Sarcomere morphogenesis in flight muscle
eLife, 2018Co-Authors: Maria Spletter, Christiane Barz, Assa Yeroslaviz, Xu Zhang, Erich Brunner, Giovanni Cardone, Konrad Basler, Adrien Bonnard, Sandra Lemke, Bianca H HabermannAbstract:Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing Sarcomeres. To study sarcomerogenesis, we have generated a transcriptomics resource of developing Drosophila flight muscles and identified 40 distinct expression profile clusters. Strikingly, most sarcomeric components group in two clusters, which are strongly induced after all myofibrils have been assembled, indicating a transcriptional transition during myofibrillogenesis. Following myofibril assembly, many short Sarcomeres are added to each myofibril. Subsequently, all Sarcomeres mature, reaching 1.5 mm diameter and 3.2 mm length and acquiring stretch-sensitivity. The efficient induction of the transcriptional transition during myofibrillogenesis, including the transcriptional boost of sarcomeric components, requires in part the transcriptional regulator Spalt major. As a consequence of Spalt knock-down, Sarcomere maturation is defective and fibers fail to gain stretch-sensitivity. Together, this defines an ordered Sarcomere morphogenesis process under precise transcriptional control-a concept that may also apply to vertebrate muscle or heart development.
-
a transcriptomics resource reveals a transcriptional transition during ordered Sarcomere morphogenesis in flight muscle
eLife, 2018Co-Authors: Maria L. Spletter, Christiane Barz, Assa Yeroslaviz, Xu Zhang, Sandra B Lemke, Adrien Bonnard, Erich BrunnerAbstract:Animals may have different types of muscles but they all have one thing in common: molecular machines called Sarcomeres that produce a pulling force. Conserved from fruit flies to humans, these structures line up end-to-end inside muscle cells, forming long cables called myofibrils. Some of the myofibrils in a human can reach several centimetres in length, which is much longer than those in a fruit fly. However, individual Sarcomeres are the same length in both humans and flies. To build the parts of the Sarcomere, an animal cell first copies the relevant genes into intermediate molecules known as mRNAs, which are then translated to build new Sarcomere proteins. Developing muscle cells later tune their Sarcomeres to make them sensitive to stretching. This tweaks the power and force of the mature muscle, but the details of this developmental process are not fully understood. Now, Spletter et al. have counted all the mRNAs in the developing flight muscles of fruit flies, with the aim of generating a resource that catalogues the changes in gene activity, or expression, that occur as muscles develop. This revealed that Sarcomeres form in three phases. First, the cells assembled all their myofibrils. Then, they added short Sarcomeres to the ends of their myofibrils. Finally, the Sarcomeres matured to their full length and diameter, and became sensitive to stretching. Fruit fly muscles had 40 patterns of gene expression, with most of the Sarcomere components having one of two specific patterns. The expression of these genes dramatically rose after the young muscle cells had finished assembling all their myofibrils, suggesting muscles express different genes when their Sarcomeres mature. A protein called spalt-major helped the cell to know when to make the transition, allowing the Sarcomeres to grow in length and width. Losing spalt-major late in muscle development stopped Sarcomere growth and prevented the tuning process. The Sarcomeres failed to become sensitive to stretching, a crucial feature of mature muscle. Muscles without spalt-major contracted too much and without coordination, like a muscle spasm. The similarities between fruit fly and human Sarcomeres suggest this developmental sequence may also occur in human muscles too. Understanding these steps may help to improve repair after injury or muscle growth during exercise. The next step is to test whether regenerating or growing muscles develop in the same way.
-
systematic transcriptomics reveals a biphasic mode of Sarcomere morphogenesis in flight muscles regulated by spalt
bioRxiv, 2017Co-Authors: Maria L. Spletter, Christiane Barz, Assa Yeroslaviz, Xu Zhang, Sandra B Lemke, Erich Brunner, Giovanni Cardone, Konrad Basler, Bianca H Habermann, Frank SchnorrerAbstract:Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing Sarcomeres. To study how Sarcomeres are built, we performed transcriptome sequencing of developing Drosophila flight muscles and identified 40 distinct expression profile clusters. Strikingly, two clusters are strongly enriched for sarcomeric components. Temporal gene expression together with detailed morphological analysis enabled us to define two distinct phases of Sarcomere development, which both require the transcriptional regulator Spalt major. During the Sarcomere formation phase, 1.8 micrometer long immature Sarcomeres assemble myofibrils that spontaneously contract. During the Sarcomere maturation phase, these Sarcomeres grow to their final 3.2 micrometer length and 1.5 micrometer diameter and acquire stretch-sensitivity. Interestingly, the final number of myofibrils per flight muscle fiber is determined at the onset of the first phase. Together, this defines a biphasic mode of Sarcomere and myofibril morphogenesis - a new concept that may also apply to vertebrate muscle or heart development.
Maria L. Spletter - One of the best experts on this subject based on the ideXlab platform.
-
a transcriptomics resource reveals a transcriptional transition during ordered Sarcomere morphogenesis in flight muscle
eLife, 2018Co-Authors: Maria L. Spletter, Christiane Barz, Assa Yeroslaviz, Xu Zhang, Sandra B Lemke, Adrien Bonnard, Erich BrunnerAbstract:Animals may have different types of muscles but they all have one thing in common: molecular machines called Sarcomeres that produce a pulling force. Conserved from fruit flies to humans, these structures line up end-to-end inside muscle cells, forming long cables called myofibrils. Some of the myofibrils in a human can reach several centimetres in length, which is much longer than those in a fruit fly. However, individual Sarcomeres are the same length in both humans and flies. To build the parts of the Sarcomere, an animal cell first copies the relevant genes into intermediate molecules known as mRNAs, which are then translated to build new Sarcomere proteins. Developing muscle cells later tune their Sarcomeres to make them sensitive to stretching. This tweaks the power and force of the mature muscle, but the details of this developmental process are not fully understood. Now, Spletter et al. have counted all the mRNAs in the developing flight muscles of fruit flies, with the aim of generating a resource that catalogues the changes in gene activity, or expression, that occur as muscles develop. This revealed that Sarcomeres form in three phases. First, the cells assembled all their myofibrils. Then, they added short Sarcomeres to the ends of their myofibrils. Finally, the Sarcomeres matured to their full length and diameter, and became sensitive to stretching. Fruit fly muscles had 40 patterns of gene expression, with most of the Sarcomere components having one of two specific patterns. The expression of these genes dramatically rose after the young muscle cells had finished assembling all their myofibrils, suggesting muscles express different genes when their Sarcomeres mature. A protein called spalt-major helped the cell to know when to make the transition, allowing the Sarcomeres to grow in length and width. Losing spalt-major late in muscle development stopped Sarcomere growth and prevented the tuning process. The Sarcomeres failed to become sensitive to stretching, a crucial feature of mature muscle. Muscles without spalt-major contracted too much and without coordination, like a muscle spasm. The similarities between fruit fly and human Sarcomeres suggest this developmental sequence may also occur in human muscles too. Understanding these steps may help to improve repair after injury or muscle growth during exercise. The next step is to test whether regenerating or growing muscles develop in the same way.
-
polarization resolved microscopy reveals a muscle myosin motor independent mechanism of molecular actin ordering during Sarcomere maturation
PLOS Biology, 2018Co-Authors: Olivier Loison, Manuela Weitkunat, Aynur Kayacopur, Camila Nascimento Alves, Till Matzat, Stefan Luschnig, Maria L. Spletter, Sophie Brasselet, Pierre-françois LenneAbstract:Sarcomeres are stereotyped force-producing mini-machines of striated muscles. Each Sarcomere contains a pseudocrystalline order of bipolar actin and myosin filaments, which are linked by titin filaments. During muscle development, these three filament types need to assemble into long periodic chains of Sarcomeres called myofibrils. Initially, myofibrils contain immature Sarcomeres, which gradually mature into their pseudocrystalline order. Despite the general importance, our understanding of myofibril assembly and Sarcomere maturation in vivo is limited, in large part because determining the molecular order of protein components during muscle development remains challenging. Here, we applied polarization-resolved microscopy to determine the molecular order of actin during myofibrillogenesis in vivo. This method revealed that, concomitantly with mechanical tension buildup in the myotube, molecular actin order increases, preceding the formation of immature Sarcomeres. Mechanistically, both muscle and nonmuscle myosin contribute to this actin order gain during early stages of myofibril assembly. Actin order continues to increase while myofibrils and Sarcomeres mature. Muscle myosin motor activity is required for the regular and coordinated assembly of long myofibrils but not for the high actin order buildup during Sarcomere maturation. This suggests that, in muscle, other actin-binding proteins are sufficient to locally bundle or cross-link actin into highly regular arrays.
-
systematic transcriptomics reveals a biphasic mode of Sarcomere morphogenesis in flight muscles regulated by spalt
bioRxiv, 2017Co-Authors: Maria L. Spletter, Christiane Barz, Assa Yeroslaviz, Xu Zhang, Sandra B Lemke, Erich Brunner, Giovanni Cardone, Konrad Basler, Bianca H Habermann, Frank SchnorrerAbstract:Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing Sarcomeres. To study how Sarcomeres are built, we performed transcriptome sequencing of developing Drosophila flight muscles and identified 40 distinct expression profile clusters. Strikingly, two clusters are strongly enriched for sarcomeric components. Temporal gene expression together with detailed morphological analysis enabled us to define two distinct phases of Sarcomere development, which both require the transcriptional regulator Spalt major. During the Sarcomere formation phase, 1.8 micrometer long immature Sarcomeres assemble myofibrils that spontaneously contract. During the Sarcomere maturation phase, these Sarcomeres grow to their final 3.2 micrometer length and 1.5 micrometer diameter and acquire stretch-sensitivity. Interestingly, the final number of myofibrils per flight muscle fiber is determined at the onset of the first phase. Together, this defines a biphasic mode of Sarcomere and myofibril morphogenesis - a new concept that may also apply to vertebrate muscle or heart development.
Erich Brunner - One of the best experts on this subject based on the ideXlab platform.
-
A transcriptomics resource reveals a transcriptional transition during ordered Sarcomere morphogenesis in flight muscle
eLife, 2018Co-Authors: Maria Spletter, Christiane Barz, Assa Yeroslaviz, Xu Zhang, Erich Brunner, Giovanni Cardone, Konrad Basler, Adrien Bonnard, Sandra Lemke, Bianca H HabermannAbstract:Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing Sarcomeres. To study sarcomerogenesis, we have generated a transcriptomics resource of developing Drosophila flight muscles and identified 40 distinct expression profile clusters. Strikingly, most sarcomeric components group in two clusters, which are strongly induced after all myofibrils have been assembled, indicating a transcriptional transition during myofibrillogenesis. Following myofibril assembly, many short Sarcomeres are added to each myofibril. Subsequently, all Sarcomeres mature, reaching 1.5 mm diameter and 3.2 mm length and acquiring stretch-sensitivity. The efficient induction of the transcriptional transition during myofibrillogenesis, including the transcriptional boost of sarcomeric components, requires in part the transcriptional regulator Spalt major. As a consequence of Spalt knock-down, Sarcomere maturation is defective and fibers fail to gain stretch-sensitivity. Together, this defines an ordered Sarcomere morphogenesis process under precise transcriptional control-a concept that may also apply to vertebrate muscle or heart development.
-
a transcriptomics resource reveals a transcriptional transition during ordered Sarcomere morphogenesis in flight muscle
eLife, 2018Co-Authors: Maria L. Spletter, Christiane Barz, Assa Yeroslaviz, Xu Zhang, Sandra B Lemke, Adrien Bonnard, Erich BrunnerAbstract:Animals may have different types of muscles but they all have one thing in common: molecular machines called Sarcomeres that produce a pulling force. Conserved from fruit flies to humans, these structures line up end-to-end inside muscle cells, forming long cables called myofibrils. Some of the myofibrils in a human can reach several centimetres in length, which is much longer than those in a fruit fly. However, individual Sarcomeres are the same length in both humans and flies. To build the parts of the Sarcomere, an animal cell first copies the relevant genes into intermediate molecules known as mRNAs, which are then translated to build new Sarcomere proteins. Developing muscle cells later tune their Sarcomeres to make them sensitive to stretching. This tweaks the power and force of the mature muscle, but the details of this developmental process are not fully understood. Now, Spletter et al. have counted all the mRNAs in the developing flight muscles of fruit flies, with the aim of generating a resource that catalogues the changes in gene activity, or expression, that occur as muscles develop. This revealed that Sarcomeres form in three phases. First, the cells assembled all their myofibrils. Then, they added short Sarcomeres to the ends of their myofibrils. Finally, the Sarcomeres matured to their full length and diameter, and became sensitive to stretching. Fruit fly muscles had 40 patterns of gene expression, with most of the Sarcomere components having one of two specific patterns. The expression of these genes dramatically rose after the young muscle cells had finished assembling all their myofibrils, suggesting muscles express different genes when their Sarcomeres mature. A protein called spalt-major helped the cell to know when to make the transition, allowing the Sarcomeres to grow in length and width. Losing spalt-major late in muscle development stopped Sarcomere growth and prevented the tuning process. The Sarcomeres failed to become sensitive to stretching, a crucial feature of mature muscle. Muscles without spalt-major contracted too much and without coordination, like a muscle spasm. The similarities between fruit fly and human Sarcomeres suggest this developmental sequence may also occur in human muscles too. Understanding these steps may help to improve repair after injury or muscle growth during exercise. The next step is to test whether regenerating or growing muscles develop in the same way.
-
systematic transcriptomics reveals a biphasic mode of Sarcomere morphogenesis in flight muscles regulated by spalt
bioRxiv, 2017Co-Authors: Maria L. Spletter, Christiane Barz, Assa Yeroslaviz, Xu Zhang, Sandra B Lemke, Erich Brunner, Giovanni Cardone, Konrad Basler, Bianca H Habermann, Frank SchnorrerAbstract:Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing Sarcomeres. To study how Sarcomeres are built, we performed transcriptome sequencing of developing Drosophila flight muscles and identified 40 distinct expression profile clusters. Strikingly, two clusters are strongly enriched for sarcomeric components. Temporal gene expression together with detailed morphological analysis enabled us to define two distinct phases of Sarcomere development, which both require the transcriptional regulator Spalt major. During the Sarcomere formation phase, 1.8 micrometer long immature Sarcomeres assemble myofibrils that spontaneously contract. During the Sarcomere maturation phase, these Sarcomeres grow to their final 3.2 micrometer length and 1.5 micrometer diameter and acquire stretch-sensitivity. Interestingly, the final number of myofibrils per flight muscle fiber is determined at the onset of the first phase. Together, this defines a biphasic mode of Sarcomere and myofibril morphogenesis - a new concept that may also apply to vertebrate muscle or heart development.
Scott L. Delp - One of the best experts on this subject based on the ideXlab platform.
-
human soleus Sarcomere lengths measured using in vivo microendoscopy at two ankle flexion angles
Journal of Biomechanics, 2016Co-Authors: Xuefeng Chen, Scott L. DelpAbstract:Abstract The forces generated by the soleus muscle play an important role in standing and locomotion. The lengths of the Sarcomeres of the soleus affect its force-generating capacity, yet it is unknown how Sarcomere lengths in the soleus change as a function of ankle flexion angle. In this study, we used microendoscopy to measure resting Sarcomere lengths at 10° plantarflexion and 20° dorsiflexion in 7 healthy individuals. Mean Sarcomere lengths at 10° plantarflexion were 2.84±0.09 µm (mean±S.E.M.), near the optimal length for Sarcomere force generation. Sarcomere lengths were 3.43±0.09 µm at 20° dorsiflexion, indicating that they were longer than optimal length when the ankle was in dorsiflexion and the muscle was inactive. Our results indicate a smaller Sarcomere length difference between two ankle flexion angles compared to estimates from musculoskeletal models and suggest why these models frequently underestimate the force-generating capacity of the soleus.
-
changes in Sarcomere lengths of the human vastus lateralis muscle with knee flexion measured using in vivo microendoscopy
Journal of Biomechanics, 2016Co-Authors: Xuefeng Chen, Mark J. Schnitzer, Gabriel N Sanchez, Scott L. DelpAbstract:Abstract Sarcomeres are the basic contractile units of muscle, and their lengths influence muscle force-generating capacity. Despite their importance, in vivo Sarcomere lengths remain unknown for many human muscles. Second harmonic generation (SHG) microendoscopy is a minimally invasive technique for imaging Sarcomeres in vivo and measuring their lengths. In this study, we used SHG microendoscopy to visualize Sarcomeres of the human vastus lateralis, a large knee extensor muscle important for mobility, to examine how Sarcomere lengths change with knee flexion and thus affect the muscle׳s force-generating capacity. We acquired in vivo Sarcomere images of several muscle fibers of the resting vastus lateralis in six healthy individuals. Mean Sarcomere lengths increased (p=0.031) from 2.84±0.16 μm at 50° of knee flexion to 3.17±0.13 μm at 110° of knee flexion. The standard deviation of Sarcomere lengths among different fibers within a muscle was 0.21±0.09 μm. Our results suggest that the Sarcomeres of the resting vastus lateralis at 50° of knee flexion are near optimal length. At a knee flexion angle of 110° the resting Sarcomeres of vastus lateralis are longer than optimal length. These results show a smaller Sarcomere length change and greater conservation of force-generating capacity with knee flexion than estimated in previous studies.
-
in vivo imaging of human Sarcomere twitch dynamics in individual motor units
Neuron, 2015Co-Authors: Gabriel N Sanchez, Scott L. Delp, Mark J. Schnitzer, Xuefeng Chen, S Sinha, Holly Liske, Viet NguyenAbstract:SUMMARY Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of Sarcomeres, skeletal muscle’s contractile units. Despite the motor unit’s centrality to neuromuscular physiology, no extant technology can image Sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of Sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the Sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In poststroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and Sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans.
-
Sarcomere lengths in human extensor carpi radialis brevis measured by microendoscopy
Muscle & Nerve, 2013Co-Authors: Melinda J Cromie, Gabriel N Sanchez, Mark J. Schnitzer, Scott L. DelpAbstract:Introduction: Second-harmonic generation micro- endoscopy is a minimally invasive technique to image sarco- meres and measure their lengths in humans, but motion artifact and low signal have limited the use of this novel technique. Methods: We discovered that an excitation wavelength of 960 nm maximized image signal; this enabled an image acquisition rate of 3 frames/s, which decreased motion artifact. We then used microendoscopy to measure Sarcomere lengths in the human extensor carpi radialis brevis with the wrist at 45 � exten- sion and 45 � flexion in 7 subjects. We also measured the variability in Sarcomere lengths within single fibers. Results: Av- erage Sarcomere lengths in 45 � extension were 2.9360.29 lm (6SD) and increased to 3.5860.19 l mi n 45 � flexion. Within single fibers the standard deviation of Sarcomere lengths in se- ries was 0.20 lm.Conclusions: Microendoscopy can be used to measure Sarcomere lengths at different body postures. Lengths of Sarcomeres in series within a fiber vary substantially. Muscle Nerve 48: 286-292, 2013
-
Minimally invasive high-speed imaging of Sarcomere contractile dynamics in mice and humans
Nature, 2008Co-Authors: Michael E. Llewellyn, Robert P. J. Barretto, Scott L. Delp, Mark J. SchnitzerAbstract:Sarcomeres are the basic contractile units of striated muscle. Uncovering how Sarcomeres change length and develop force is fundamental to understanding biomechanics, muscle physiology, and neuromuscular control. Llewellyn et al. describe the use of optical microendoscopy to visualize Sarcomeres and their micrometre-scale motions in live mice and humans, revealing unanticipated local variations in Sarcomere lengths. Imaging of human Sarcomeres is expected to enable advances in biomechanical modelling, orthopaedic therapeutics, and the understanding and treatment of neuromuscular disorders. This paper describes the use of optical microendoscopy to visualize Sarcomeres and their micron-scale motions in live mice and humans, revealing unanticipated local variations in Sarcomere lengths. Imaging of human Sarcomeres is expected to enable advances in biomechanical modelling, orthopedic therapeutics, and the understanding and treatment of neuromuscular disorders Sarcomeres are the basic contractile units of striated muscle. Our knowledge about Sarcomere dynamics has primarily come from in vitro studies of muscle fibres1 and analysis of optical diffraction patterns obtained from living muscles2,3. Both approaches involve highly invasive procedures and neither allows examination of individual Sarcomeres in live subjects. Here we report direct visualization of individual Sarcomeres and their dynamical length variations using minimally invasive optical microendoscopy4 to observe second-harmonic frequencies of light generated in the muscle fibres5,6 of live mice and humans. Using microendoscopes as small as 350 μm in diameter, we imaged individual Sarcomeres in both passive and activated muscle. Our measurements permit in vivo characterization of Sarcomere length changes that occur with alterations in body posture and visualization of local variations in Sarcomere length not apparent in aggregate length determinations. High-speed data acquisition enabled observation of Sarcomere contractile dynamics with millisecond-scale resolution. These experiments point the way to in vivo imaging studies demonstrating how Sarcomere performance varies with physical conditioning and physiological state, as well as imaging diagnostics revealing how neuromuscular diseases affect contractile dynamics.
